Diagnostic markers for ischemia

Abstract

This invention relates to the diagnosis and monitoring of ischemia, including but not limited to myocardial and cerebral ischemia, by measuring the concentration of molecules that do not originate from the ischemic tissue but whose concentration in the blood and other fluids changes as a consequence of the ischemic state.

What is claimed is: 
     
       1. A method of detecting an ischemic condition in a mammal comprising the steps of:
 (a) measuring a level of an ischemic marker which is an unbound or water-soluble lipid in a test sample from a fluid of said mammal; 
 (b) comparing the measured level of said ischemic marker and a predetermined value for the level of said marker; and 
 (c) determining if the level of said ischemic marker measured in said test sample correlates with an ischemic condition in said mammal, 
 wherein said predetermined value for the level of said marker is indicative of the non-ischemic condition and wherein the ischemic marker measured is soluble in an aqueous buffer. 
 
     
     
       2. The method according to  claim 1 , wherein the mammal is a human. 
     
     
       3. The method according to  claim 2 , wherein the fluid is selected from the group consisting of blood, serum, plasma, saliva, bile, gastric juices, cerebral spinal fluid, lymph, interstitial fluid and urine. 
     
     
       4. The method according to  claim 3 , wherein the fluid is blood. 
     
     
       5. The method according to  claim 1 , wherein the lipid is a fatty acid. 
     
     
       6. The method according to  claim 1 , wherein a heart is ischemic. 
     
     
       7. The method according to  claim 1 , wherein the ischemic marker is detected by UV/VIS, infrared, microwave, radio, absorption or fluorescence spectroscopy. 
     
     
       8. The method of  claim 1 , further comprising an initial step of selecting a mammal presenting symptoms of ischemia. 
     
     
       9. The method of  claim 1 , further comprising the step of administering anti-ischemic therapy if the level of ischemic marker correlates with ischemia in said mammal. 
     
     
       10. The method of  claim 9 , wherein the anti-ischemic therapy comprises a means to lower levels of serum fatty acids. 
     
     
       11. The method of  claim 9 , wherein the anti-ischemic therapy is reperfusion therapy, antithrombolytic therapy, angiogenic therapy or surgery. 
     
     
       12. The method of determining ischemia according to  claim 1 , wherein the ischemic marker is an unbound or water-soluble free fatty acid. 
     
     
       13. The method according to  claim 12 , wherein the unbound or water-soluble free fatty acid is detected by a protein that binds fatty acid. 
     
     
       14. The method according to  claim 13 , wherein said protein that binds an unbound or water-soluble free fatty acid is fluorescent and exhibits a fluorescence that is different when the fatty acid is bound than when it is not bound. 
     
     
       15. The method according to  claim 14 , wherein the protein is one of the family of intracellular Fatty Acid Binding Proteins (FABPs) that have molecular weights between about 13,000 and 16,000 Dalton. 
     
     
       16. The method according to  claim 15 , wherein the FABP is a rat intestinal FABP. 
     
     
       17. The method according to  claim 16 , wherein the FABP is ADIFAB. 
     
     
       18. The method according to  claim 17 , wherein the acrylodan-labeled FABP is ADIFAB2. 
     
     
       19. The method according to  claim 13 , wherein the protein is albumin. 
     
     
       20. The method according to  claim 19 , wherein the albumin is covalently labeled with 7-hydroxycoumarin or anthraniloyl. 
     
     
       21. The method according to  claim 12 , wherein a level of the unbound or water-soluble free fatty acid greater than 2 standard deviation units above an average value of a level of the unbound or water-soluble free fatty acid determined from a non-ischemic population is indicative of the ischemic condition. 
     
     
       22. The method according to  claim 12 , wherein a level of the unbound or water-soluble free fatty acid greater than about twice an average value of a level of the unbound or water-soluble free fatty acid determined from a non-ischemic population is indicative of the ischemic condition. 
     
     
       23. The method according to  claim 12 , wherein a level of the unbound or water-soluble free fatty acid greater than about 2.5 nM is indicative of the ischemic condition. 
     
     
       24. The method of determining ischemia according to  claim 1 , wherein the ischemic marker is total unbound free fatty acid. 
     
     
       25. The method according to  claim 24 , wherein a level of the total unbound free fatty acid greater than 2 standard deviation units above an average value for the level of the total free fatty acid determined from a non-ischemic population is indicative of the ischemic condition. 
     
     
       26. The method according to  claim 24 , wherein a level of the total unbound free fatty acid greater than about twice an average value of a level of the total free fatty acid determined from a non-ischemic population is indicative of the ischemic condition. 
     
     
       27. The method according to  claim 24 , wherein the ischemic marker is a ratio of total unbound free fatty acid to albumin. 
     
     
       28. The method according to  claim 27 , wherein the ratio of total unbound free fatty acid to albumin greater than about two standard deviation units above an average value of the ratio of total free fatty acid to albumin determined from a non-ischemic population is indicative of the ischemic condition. 
     
     
       29. The method according to  claim 27 , wherein the ratio of total unbound free fatty acid to albumin greater than about twice an average value of the ratio of total free fatty acid to albumin determined from a non-ischemic population is indicative of the ischemic condition.